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Biomedical subjects

Karsten Witt

Publications and source records attributed to Karsten Witt.

9 recordsLinked to original sources
PubMed2006

The impact of normal aging and Parkinson's disease on response preparation in task-switching behavior.

This study investigates the ability to use foreknowledge in preparation of cognitive processes in young and older participants and in PD patients. Additionally, we test the hypothesis that age-associated cognitive deficits in task switching reflect a dopaminergic dysfunction that accompanies healthy aging. To this end, we use a task-switching paradigm that (i) is known to be highly sensitive for dopaminergic dysfunction in the frontostriatal loops and (ii) can be applied with predictable and unpredictable switch and non-switch trials to assess the effect of task foreknowledge. Our results show that young participants benefit from foreknowledge and are thus able to prepare for predictable cognitive processes. Older participants have lost their ability to benefit from foreknowledge, which seems to be an effect of healthy aging. In predictable trials, the performance of PD patients did not differ from that of controls. Thus, PD patients do not show an additional deficit in the preparation of predictable cognitive switches. However, PD patients are specifically impaired in unpredictable trials compared to controls. We suggest that this result can be explained by the uncertainty about the next task in the unpredictable condition which prevents an automatic process and demands more attention. Furthermore, our results of older participants do not resemble the deficits seen in PD patients in task-switching behavior. This argues for different mechanisms that underlie the changes in task-switching behavior in healthy aging and PD.

Adult↗
PubMed2006

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.

Aged↗
PubMed2006

Effects of smoking on the pharmacokinetics of erlotinib.

PURPOSE: To compare the pharmacokinetic variables of erlotinib in current smokers with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib. EXPERIMENTAL DESIGN: This was a single-center, open-label pharmacokinetic study in healthy male subjects. Subjects were enrolled into two treatment cohorts based on smoking status (current smokers and nonsmokers). The pharmacokinetic profile for erlotinib and its metabolite, OSI-420, was determined for each subject following each treatment. RESULTS: Current smokers achieved significantly less erlotinib exposure following a single 150 or 300 mg dose than nonsmokers. Following the 150 mg dose, the geometric mean erlotinib AUC(0-infinity) in smokers was 2.8-fold lower than in nonsmokers and similar to that of nonsmokers at the 300 mg dose. C(max) in smokers was two-thirds of that in nonsmokers, and C(24h) in smokers was 8.3-fold lower than in nonsmokers. The median C(24h) of smokers at the 300 mg dose was slightly less than the C(24h) of smokers at the 150 mg dose. The median C(max) was greater in smokers at the 300 mg dose than in nonsmokers at the 150 mg dose. CONCLUSION: This study confirms that the pharmacokinetics of erlotinib is different in current smokers and nonsmokers. The observation that AUC(0-infinity) and C(24h) were significantly decreased in smokers compared with nonsmokers, and a smaller decrease in C(max) was observed, is consistent with increased metabolic clearance of erlotinib in current smokers.

Adult↗
PubMed2006

Subthalamic nucleus influences spatial orientation in extra-personal space.

While the role of frontal and parietal cortex in spatial orientation has been studied extensively, the contribution of the basal ganglia and especially the subthalamic nucleus to spatial orientation remains less clear. Here we use subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) as a reversible model of functional lesioning to evaluate the influence of the STN in extra-personal space orientation. To this end, 12 PD patients were examined 1 year after implantation of DBS electrodes in the STN after overnight withdrawal of L-dopa. Patients were tested in a pseudo-randomized order while both stimulators, the right only, the left only, or no stimulator, were switched on. Patients performed line bisection and a reaction time task responding to stimuli of the middle, the left, and the right extra-personal space. A separate assessment of the right and left hand responding to visual stimuli in each hemispace made it possible to distinguish hemi-spatial and hemi-motor impairments. No asymmetries in space orientation were found when both stimulators were switched OFF, when both stimulators were switched ON, and when only the right stimulator was switched ON. When only the left subthalamic stimulation was switched ON, the reaction times of both hands to visual stimuli in the left extra-personal hemispace increased significantly and the line bisection test showed a significant orientation to the right. These results lead to the conclusion that the STN and its cortical projections influence the network involved in visuospatial orientation. These patterns of symptoms of neglect demonstrate the influence of the STN on the attentional system of the nondominant hemisphere.

Attention↗
PubMed2006

Differential effects of L-dopa and subthalamic stimulation on depressive symptoms and hedonic tone in Parkinson's disease.

Patients with Parkinson's disease frequently have mild to moderate depression and exhibit low hedonic tone. The authors investigate the impact of a single L-dopa challenge and the acute effects of electric stimulation of the subthalamic nucleus (STN) on symptoms of depression and hedonic tone. Depressive symptoms improved with L-dopa and STN stimulation to the same extent. However, hedonic tone improved only with L-dopa. Most of the emotional changes did not correlate with changes in motor performance, indicating they were not just reactive but specific to the treatment. These results demonstrate a single dissociation of depressive symptoms and anhedonia in response to an acute L-dopa and STN-stimulation challenge.

Affect↗
PubMed2004

Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease. Although several studies have assessed cognitive functions before surgery and after long-term STN stimulation, only a few have assessed patients while stimulation is on and off to more specifically address the short-term cognitive effects of STN deep brain stimulation. OBJECTIVE: To examine the short-term effects of STN stimulation on several tests sensitive to executive function and the long-term effects of STN stimulation on a global cognitive scale. DESIGN: Twenty-three patients with Parkinson disease were tested 6 to 12 months after surgery with STN stimulation switched on and off in a random order while taking their regular medication. The Unified Parkinson's Disease Rating Scale motor score was also rated in the on and off stimulation condition. The neuropsychological battery included digit span, verbal fluency, Stroop color test, and random number generation in a single- and dual-task condition. RESULTS: Short-term stimulation improved the results on the Random Number Generation Task, requiring suppression of habitual responses, but induced more errors in the interference task of the Stroop color test. Digit span, verbal fluency, and dual-task performance results did not change. There was a significant correlation (r = 0.47, P =.02) between improved performance on the Random Number Generation Task and impaired response inhibition in the Stroop interference condition. A preoperative to postoperative comparison showed no changes in global cognitive function with long-term STN deep brain stimulation. CONCLUSIONS: Short-term STN stimulation improves cognitive flexibility (giving up habitual responses) but impairs response inhibition. Long-term STN stimulation does not change global cognitive function.

Cognition↗
PubMed2003

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces akinesia in Parkinson's disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L-dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS-items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L-dopa test than in the pure STN-DBS condition. Other akinesia items and the time for build-up of lifting force were equally improved in both conditions. This suggests that routine STN-DBS might not be equally effective on all aspects of fine motor functions.

Antiparkinson Agents↗